1. Proinflammatory Cytokines in the Course of Mycobacterium tuberculosis--Induced Apoptosis in Monocytes/Macrophages.
- Author
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Ciaramella, A., Cavone, A., Santucci, M.B., Amicosante, M., Martino, A., Auricchio, G., Pucillo, L.P., Colizzi, V., and Fraziano, M.
- Subjects
APOPTOSIS ,MYCOBACTERIUM tuberculosis ,TUMOR necrosis factors - Abstract
Mycobacterium tuberculosis (MTB) can induce apoptosis in monocytes/macrophages both in vitro and in vivo, and this phenomenon is associated with mycobacterial survival. The present study addresses the possibility that apoptotic and inflammatory pathways could coexist through a caspase-l-mediated mechanism. In this context, a caspase-1 inhibitor (YVAD), but not caspase-3 (DEVD) or caspase-4 (LEVD) inhibitors, was able to strongly inhibit MTBinduced apoptosis. Moreover, caspase-1 activity was confirmed by the increased maturation of interleukin (IL)-1β. Of interest, IL-1β and tumor necrosis factor (TNF)-α were produced massively in the course of infection, and both were inhibited by YVAD pretreatment. To determine whether TNF-α was produced actively by apoptotic cells, the intracytoplasmatic cytokine content and apoptotic phenotype were analyzed at the single-cell level. Results showed a progressive increase of TNF-α production in annexin V-positive cells. These results indicate that MTB-induced apoptosis is associated with proinflammatory cytokine production. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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